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用整合缺陷型慢病毒载体-猴免疫缺陷病毒-群特异性抗原（IDLV-SIV-Gag）进行治疗性疫苗接种可使慢性感染猿猴免疫缺陷病毒的猕猴的病毒血症得到持久控制。

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

作者信息

Blasi Maria, Wescott Elizabeth C, Baker Erich J, Mildenberg Benjamin, LaBranche Celia, Rountree Wes, Haynes Barton F, Saunders Kevin O, Moody M Anthony, Negri Donatella, Santra Sampa, Cara Andrea, Klotman Mary E

机构信息

1Department of Medicine, Duke University Medical Center, Durham, NC USA.

2Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC USA.

出版信息

NPJ Vaccines. 2020 May 8;5(1):36. doi: 10.1038/s41541-020-0186-5. eCollection 2020.

DOI:10.1038/s41541-020-0186-5
PMID:32411399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7210278/
Abstract

Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. Further, HIV-infected individuals reliably exhibit viral rebound when ART is interrupted, suggesting that the host immune response fails to control viral replication in persistent reservoirs. Therapeutic vaccines are one current approach to improving antiviral host immune responses and enhance long term virus control. In the present study, we used an integrase defective lentiviral vector (IDLV) expressing SIV-Gag to boost anti-Gag specific immune responses in macaques chronically infected with the tier-2 SHIV-1157(QNE)Y173H. A single immunization with IDLV-SIV-Gag induced durable (>20 weeks) virus control in 55% of the vaccinated macaques, correlating with an increased magnitude of SIV-Gag specific CD8+ T-cell responses. IDLV-based therapeutic vaccines are therefore an effective approach to improve virus specific CD8+ T-cell responses and mediate virus control.

摘要

尽管付出了巨大的科学努力，但目前仍无法治愈艾滋病毒感染。抗逆转录病毒治疗（ART）虽然可以帮助控制病毒并预防传播，但无法从治疗开始前就已建立的病毒库中根除艾滋病毒。此外，艾滋病毒感染者在中断抗逆转录病毒治疗后会可靠地出现病毒反弹，这表明宿主免疫反应无法控制持续存在的病毒库中的病毒复制。治疗性疫苗是目前改善抗病毒宿主免疫反应并增强长期病毒控制的一种方法。在本研究中，我们使用表达SIV-Gag的整合酶缺陷型慢病毒载体（IDLV）来增强慢性感染2级SHIV-1157（QNE）Y173H的猕猴的抗Gag特异性免疫反应。用IDLV-SIV-Gag进行单次免疫在55%的接种猕猴中诱导了持久（>20周）的病毒控制，这与SIV-Gag特异性CD8 + T细胞反应的增强幅度相关。因此，基于IDLV的治疗性疫苗是改善病毒特异性CD8 + T细胞反应并介导病毒控制的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/8fee9c2ee232/41541_2020_186_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/2938b3ad9ef2/41541_2020_186_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/7489c9797fbe/41541_2020_186_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/99a6980d34e5/41541_2020_186_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/8fee9c2ee232/41541_2020_186_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/2938b3ad9ef2/41541_2020_186_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/7489c9797fbe/41541_2020_186_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/d5626ef36a3b/41541_2020_186_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/99a6980d34e5/41541_2020_186_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2209/7210278/8fee9c2ee232/41541_2020_186_Fig5_HTML.jpg

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